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Flashcards in Antifungals Deck (22)
1

How does the -azole group work?

Inhibit C14 alpha demethylase needed for cell membrane ergosterol synthesis by fungi (ie acts in the ER)


Posaconazole kills zygomycetes AND IS SUPERIOR COMPARED WITH FLUCONAZOLE FOR PROPHYLAXIS AGAINST INVASIVE FUNGAL INFECTIONS IN HIGH RISK PATIENTS. Does not kill Sporothrix

2

Voriconazole side effect?

Transient visual disturbance
Asymptomatic hepatic enzymes up
DRUG INTERACTIONS

Good for Aspergillus, candida, scedosporium, fusarium

3

Amphotericin B mechanism? (polyene)

Inserts into cell membrane which increases permeability and all the potassium and intracellular components leak out

Fungicidal
Causes HYPOKALAEMIA

Aspergillus, Candida except lusitaniae
Covers glabrata and krusei
Can treat zygomycosis and fusariosis

Note that Nystatin are polyenes

4

Why do you give lipophilic ambisome?

Less nephrotoxic and greater CNS penetration

Works by liposome preferentially binding fungal cell wall and amphotericin B released to bind ergosterols in the cell membrane forming pores.

Decreases GFR, direct vasoconstriction of afferent arterioles
K, Mg, HCO3 wasting

5

How do echinocandins work?

eg Anidulafungin, Micafungin, Caspofungin (empiric therapy in feb/neut, treat candida infections)

Inhibit glucan synthase which is needed for production of beta 1,3 glucan in fungal cell walls

Cover candida and aspergillosis but not cryptococcus or non-aspergillus moulds

6

Flucytosine mechanism?

Deaminated to 5-FU-->inhibitor of thymidylate synthetase (DNA synthesis)

Work against candida and in combination with Amphotericin for cryptococcus

7

Alemtuzumab incrases rate of which infections?

Ab against CD52
used in CLL or cutaneous T cell lumphoma

Increases mould infections, CMV, PCP

8

What causes PML?

JC virus
natalizumab

Humanised monoclonal antibody against alpha 4 integrin

9

Splenectomy when can you vaccinate?

Vaccinate pre-operatively or 2 weeks post op

10

When can you re-vaccinate following BMT?

6 months post auto
12 months post allo

11

What is the best marker of risk of transmission of HBV after occupational exposure?

HBeAg status of source
Risk actually quite high- 30-50%

12

Allylamines MOA?

eg terbinafine

Inhibit fungal ergosterol synthesis at an earlier stage than the azoles

13

Fluconazole covers...

Most candida except glabrata and krusei (dose dependent)
Could use for candidaemia in non neutropaenic and haemodynamically stable patients

NO mould activity
Does cover cryptococcus so need to give after the 5FC/ambisome finished

14

Itraconazole covers...

Fluconazole + aspergillus + histoplasmosis

15

Voriconazole covers...

Candida including Krusei
Aspergillus
Fusarium (unlike ambisome)
Scedosporium (unlike ambisome)

16

Posaconazole covers...

As vori + zygomycetes
Only oral admin

BETTER THAN fluconazole for prophylaxis in terms of mortality rate

17

Echinocandins cover...

Candida
Aspergillus
NOT cryptococcus
NOT any non aspergillus moulds
NOT zygomycetes

Used in treatment of IC in neutropaenic patients and in C glabrata infection

18

Candidaemia treatment options...

If immunocompetent, fluconazole, voriconazole, ambisome, capsofungin,

If neutropaenic, capsofungin or liposomal amphotericin B

19

Invasive aspergillosis

Voriconazole first line

20

Zygomycoses

Reverse underlying condition
Debride
High dose amphotericin B

Followed by posaconazole as sequential

21

Which ones get drug level monitoring?

Posiconazole level
Voriconazole level

22

What is galactomannin antigen testing?

A polysaccharide, sometimes comes up in serum before culture of aspergillus in blood.
Can get false positive on Tazocin and false positive from presence of other fungi

HIGH neg predictive value but low positive predictive value